STOCKHOLM, SWEDEN – Adding an experimental antibody-drug conjugate to bendamustine and rituximab more than doubled overall survival over bendamustine/rituximab alone in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), investigators reported.
Among 80 transplant-ineligible patients with relapsed or refractory DLBCL in a, the combination of the antibody-drug conjugate (ADC) polatuzumab vedotin plus bendamustine/rituximab (BR) was associated with a 40% complete response rate, compared with 15% for BR alone.
More importantly, the ADC was associated with 6.7 months median progression-free survival (PFS) versus 2 months for BR, and 11.8 months median overall survival (OS), versus 4.7 months for BR alone, reported Laurie Sehn, MD, from BC Cancer in Vancouver, British Columbia, Canada.
“This randomized phase 2 trial really is, so far, the only head-to-head comparison of a novel targeted agent against a standard therapy in this patient population that’s ineligible for transplant, and it demonstrated that the combination polatuzumab vedotin with BR significantly improved the response rates and progression-free survival, as well as overall survival,” she said at the annual congress of the European Hematology Association.
However, in a separate cohort of patients with follicular lymphoma in the same trial, there was no difference in either PFS or OS during follow-up to date, Dr. Sehn reported.
Polatuzumab vedotin consists of an antibody targeted against CD79b, an antigenic protein expressed on the surface of normal B cells, as well as DLBCL and follicular lymphoma cells.
Dr. Sehn and her colleagues enrolled 80 patients with DLBCL for whom first-line chemoimmunotherapy had failed and who were ineligible for stem cell transplant due to age and/or comorbidities.
A second cohort included 80 patients with follicular lymphoma. In this group, median PFS with polatuzumab vedotin/BR was 17 months versus 17.3 months for BR alone, and median overall survival had not been reached in either arm at the time of the data cutoff.
In the DLBCL cohort, patients were randomized to receive polatuzumab vedotin 1.8 mg/kg plus bendamustine 90mg/m2 for 2 days and rituximab 375mg/m2) or BR alone for six 21-day cycles.
The complete response rate by PET scan – the primary endpoint – was significantly higher with polatuzmab/BR at 40% versus 15% for BR alone (P = .012). Respective overall response rates were 45% versus 18% (P = .008). Also, median PFS with the polatuzmab/BR therapy was 6.7 months versus 2.0 months for BR alone, translating into a hazard ratio of 0.31 (P less than .0001).
Respective median overall survival was 11.8 versus 4.7 months, translating into a hazard ratio for the polatuzmab/BR combination of 0.35 (P = .0008).
The PET complete response rates were higher with polatuzmab/BR regardless of prior lines of therapy or refractory status, Dr. Sehn noted.
“In terms of the safety, I think importantly in the combination there were no unexpected toxicities, so typical to what we would expect with what’s known with this drug alone,” Dr. Sehn said.
Grade 3 or greater toxicities that were higher with the polatuzmab/BR combination included cytopenias, febrile neutropenia, and infections. The single serious adverse event that had a higher incidence in the polatuzumab/BR arm was febrile neutropenia (DLBCL). In total, 12% of patients in the polatuzumab-containing arm and 11% of patients in the BR-only arm died on study. Many of the deaths were due to disease progression.
Anton Hagenbeek, MD, PhD, from the Academic Medical Center at the University of Amsterdam, the Netherlands, who moderated the briefing but was not involved in the study, said that about 20%-30% of patients with relapsed/refractory DLBCL are positive for the CD33 antigen, the target of brentuximab vedotin (Adcetris), and noted that this agent is also being tested in a phase 2 trial.
Martin Hutchings, MD, PhD, from Rigshospitalet in Copenhagen, the Netherlands, who co-moderated the oral abstract session, commented that “it’s not so often that we see significant overall survival differences in a phase 2 study with 80 patients.”
Based on the results of this trial, polatuzumab has been granted breakthrough therapy designation by the U.S. Food and Drug Administration and a PRIME (priority medicine) designation from the European Medicines Agency.
SOURCE: Sehn LH et al. EHA Congress, Abstract S802.